全文获取类型
收费全文 | 150篇 |
免费 | 28篇 |
出版年
2021年 | 4篇 |
2020年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 5篇 |
2012年 | 15篇 |
2011年 | 11篇 |
2010年 | 11篇 |
2009年 | 7篇 |
2008年 | 16篇 |
2007年 | 9篇 |
2006年 | 13篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 6篇 |
2002年 | 8篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 3篇 |
1980年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有178条查询结果,搜索用时 437 毫秒
51.
52.
53.
To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes. 相似文献
54.
55.
Dollive S Peterfreund GL Sherrill-Mix S Bittinger K Sinha R Hoffmann C Nabel C Hill DA Artis D Bachman MA Custers-Allen R Grunberg S Wu GD Lewis JD Bushman FD 《Genome biology》2012,13(7):R60
ABSTRACT: Eukaryotic microorganisms are important but understudied components of the human microbiome. Here we present a pipeline for analysis of deep sequencing data on single cell eukaryotes. We designed a new 18S rRNA gene specific PCR primer set and compared a published rRNA gene internal transcribed spacer (ITS) gene primer set. Amplicons were tested against 24 specimens from defined eukaryotes and eight well-characterized human stool samples. A software pipeline (https://sourceforge.net/projects/brocc/) was developed for taxonomic attribution, validated against simulated data, and tested on pyrosequence data. This study provides a well-characterized tool kit for sequence-based enumeration of eukaryotic organisms in human microbiome samples. 相似文献
56.
57.
Josiah Petersen Mary Jane Drake Emily A. Bruce Amber M. Riblett Chukwuka A. Didigu Craig B. Wilen Nirav Malani Frances Male Fang-Hua Lee Frederic D. Bushman Sara Cherry Robert W. Doms Paul Bates Kenneth Briley Jr. 《PLoS pathogens》2014,10(2)
The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV). Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P) of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection. 相似文献
58.
Papapetrou EP Lee G Malani N Setty M Riviere I Tirunagari LM Kadota K Roth SL Giardina P Viale A Leslie C Bushman FD Studer L Sadelain M 《Nature biotechnology》2011,29(1):73-78
Realizing the therapeutic potential of human induced pluripotent stem (iPS) cells will require robust, precise and safe strategies for genetic modification, as cell therapies that rely on randomly integrated transgenes pose oncogenic risks. Here we describe a strategy to genetically modify human iPS cells at 'safe harbor' sites in the genome, which fulfill five criteria based on their position relative to contiguous coding genes, microRNAs and ultraconserved regions. We demonstrate that ~10% of integrations of a lentivirally encoded β-globin transgene in β-thalassemia-patient iPS cell clones meet our safe harbor criteria and permit high-level β-globin expression upon erythroid differentiation without perturbation of neighboring gene expression. This approach, combining bioinformatics and functional analyses, should be broadly applicable to introducing therapeutic or suicide genes into patient-specific iPS cells for use in cell therapy. 相似文献
59.